We plan to examine two important aspects of growth hormone (GH) secretion. First, we propose to study the role of serotonin in releasing GH directly from the pituitary. Second, we will examine the role of GH and of somatomedin in the autoregulation of GH secretion, and investigate whether the hypothalamus plays a role in this process. We have recently demonstrated that physiologic concentrations of serotonin release significant amounts of GH directly from the rat adenohypophysis in vitro. This raises the possibility that serotonin within the pituitary may function as a paraendocrine regulator of GH secretion. To investigate this possibility, we will determine whether serotonergic receptor blockade or inhibition of serotonin synthesis can decrease basal GH secretion by the rat adenohypophysis in vitro in a perifusion system, or blunt the GH releasing effect of several stimulatory factors, including a partially purified extract of medium in which rat hypothalami have been incubated, that contains growth hormone releasing factor (GHRF) activity but is devoid of serotonin. Further, we will assess the physiologic characteristics of the putative serotonin receptor in the pituitary by attempting to block serotonin-induced GH secretion with different classes of receptor antagonists in our cell culture system, using primary monolayer cultures of enzymatically and mechanically dispersed rat adenchypophyseal cells. In addition, an attempt will be made to identify a receptor for serotonin in preparations of bovine pituitary membranes. In our investigation of autoregulation of GH secretion, we will determine whether either GH or multiplication stimulating activity (MSA), a specific and purified somatomedin, can suppress pituitary secretion of GH in vitro either directly or through an effect on the hypothalamus. This study will be accomplished using a single and a double perifusion apparatus. If GH or MSA suppress GH secretion via the hypothalamus, we will try and determine whether this is due to an increase in somatostatin or a decrease in GHRF secretion.